Chronic infection with either Wuchereria bancrofti or Brugia malayi many times leads to severe pathologic conditions which may culminate in elephantiasis of limbs and genitals. This pathology is to a great extent mediated by the host's inflammary response to the parasite. Despite measurable humoral and cell-mediated immune responses to the parasite, only partial protection is achieved after repeated exposure to the parasite. Drug treatment often produces severe side effects resulting from the host's inflammatory response to the dead and dying worms. Immunologic diagnostic techniques are often ineffective because of false positive and false negative reactions observed. The need for improved therapy and diagnosis of this chronic infection is obvious. This proposal is concerned with one aspect of the immunology of filarial worm infections, the characterization of circulating antibody, parasite antigen and immune complexes in the infected host. The presence of circulating antigen may account for (1) the low levels of free antibody observed even in heavy infections and (2) the false negative responses often obtained when using serologic diagnosis procedures. The detection of circulating antigen rather than circulating antibody may prove to be a more specific and sensitive diagnostic test. Circulating immune complexes may stimulate pathologic sequelae especially in the kidneys. Once the circulating antigens and immune complexes have been characterized the project can be extended to (1) an analysis of their role in the pathology and immune response during this infection and (2) their use in improved diagnostic procedures.